Patients with typhoid fever were studied to determine whether disseminated intravascular coagulation (DIC), circulating bacteria, and endotoxemia were responsible for the signs and symptoms of their illnesses. Coagulation tests in 28 patients detected thrombocytopenia in 17, hypofibrinogenemia in nine, and elevated titers of fibrinogen-related antigens in 20. Repeated testing during convalescence showed a return toward normal values. Intestinal bleeding, however, did not correlate with abnormalities of coagulation tests. Thus, DIC occurred commonly but appeared to be a subclinical event in these patients. In 25 patients with positive blood cultures for Salmonella typhi, quantitative cultures detected from less than 10 to 9 x 10(2) bacteria/ml. Limulus tests for endotoxin in plasma were negative in all 21 patients tested. These results indicated that the concentrations of circulating bacteria and endotoxin in typhoid fever are lower than in other Gram-negative bacterial infections and suggested that circulating bacteria and endotoxin do not play a major role in the pathogenesis of typhoid fever.